Age-related medical decision limits for urinary free (unconjugated) metadrenalines, catecholamines and metabolites in random urine specimens from children

Ann Clin Biochem. 2011 Jul;48(Pt 4):358-66. doi: 10.1258/acb.2011.011023. Epub 2011 Jun 13.


Background: Neuroblastoma is the most common extracranial solid tumour in childhood (8% of all childhood cancers), the most frequently diagnosed in infancy, and has one of the highest death rates, while chromaffin tumours rarely present in childhood. Both tumour types produce catecholamines and their metabolites. It is difficult to produce reference ranges for tests in children, and currently, no age-related medical decision limits for free metadrenalines (free metanephrines) in random urine specimens exist in the paediatric literature.

Methods: Results of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid, homovanillic acid (HVA), noradrenaline (NA), adrenaline, dopamine (DA), free normetadrenaline (fNMA), free metadrenaline and free 3-methoxytyramine (f3MT) in 1658 random urines obtained from infants, children and young adults were measured by high performance liquid chromatography with electrochemical detection. Specimens were excluded from consideration if obtained from the following categories, i.e. (a) harbouring neuroblastic, chromaffin, carcinoid or other tumours or malignancies; (b) medical conditions having known association with excess catecholamine excretion; (c) patients administered catecholamine or paracetamol; (d) overly dilute urine; and (e) manifesting outlying values following visual inspection.

Results: There remained 872 specimens that were grouped into seven age ranges (<1; 1 or 2; 3 or 4; 5-7; 8-10; 11-13; 14-19 y) for which medical decision limits were determined for each analyte. There was no significant difference between the results for boys or girls. In 55 patients harbouring neuroblastic tumours, HVA (54/55), f3MT (14/16), VMA (45/53) and DA (43/53) were the most frequently elevated analytes at time of diagnosis. In 11 patients presenting in childhood with chromaffin tumours, fNMA (11/11) followed by NA (10/11) were the most frequently elevated. Discussion The likely reasons for outlying or missing values, together with the reasons for variation in the distinctive biochemical patterns of analytes exhibited in individuals harbouring either neuroblastic or chromaffin tumours are discussed.

MeSH terms

  • Adolescent
  • Age Factors
  • Catecholamines / urine*
  • Child, Preschool
  • Decision Making
  • Diagnosis, Differential
  • Dopamine / urine
  • Epinephrine / urine
  • Female
  • Homovanillic Acid / urine
  • Humans
  • Infant
  • Infant, Newborn
  • Islets of Langerhans / pathology
  • Male
  • Metanephrine / urine*
  • Neuroblastoma / diagnosis*
  • Neuroblastoma / urine
  • Norepinephrine / urine
  • Pancreatic Neoplasms / diagnosis
  • Pheochromocytoma
  • Vanilmandelic Acid / urine
  • Young Adult


  • Catecholamines
  • Metanephrine
  • Vanilmandelic Acid
  • Dopamine
  • Norepinephrine
  • Homovanillic Acid
  • Epinephrine

Supplementary concepts

  • Islet cell tumor syndrome